ABSTRACT
A hitherto unknown class of C4-symmetric Caryl-Cß (C3, C8, C13, C18) axially chiral porphyrins has been synthesized and the application of their iridium (Ir) complexes in catalytic asymmetric C(sp3)-H functionalization is documented. Cyclotetramerization of enantioenriched axially chiral 2-hydroxymethyl-3-naphthyl pyrroles under mild acidic conditions affords, after oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the C4-symmetric α,α,α,α-atropenantiomer as an only isolable diastereomer. Both regioisomeric Ir(Por*)(CO)(Cl) complexes catalyze the carbene C-H insertion reaction affording the same enantiomer, albeit with slight difference in enantioselectivity. With the optimum Ir-complex 3 e, the 2-substituted arylacetic acid derivatives were generated from diazo compounds and cyclohexadiene in excellent yields and enantioselectivities.
ABSTRACT
Coumarins and 2H-pyran derivatives are among the most commonly found structural units in natural products. Therefore, the introduction of 2H-pyran moiety into the coumarin structural unit, i.e., dihydrocoumarin-fused dihydropyranones, is a potentially successful route for the identification of novel bioactive structures, and the synthesis of these structures has attracted continuing research interest. Herein, a chiral tertiary amine catalyzed [4 + 2] cyclization of 3-aroylcoumarines with benzyl 2,3-butadienoate was reported. In the presence of Kumar's 6'-(4-biphenyl)-ß-iso-cinchonine, the desired dihydrocoumarin-fused dihydropyranone products could be obtained in up to 97% yield and 90% ee values.
Subject(s)
Amines/chemistry , Coumarins/chemistry , Diacetyl/chemistry , Catalysis , Cyclization , Molecular Structure , StereoisomerismABSTRACT
The first highly enantioselective construction of chiral cyclopropa[c]coumarins was described. Using commercially available (bis)cinchona alkaloid (DHQ)2PYR as the chiral Lewis base catalyst, together with Cs2CO3 as the achiral base, the reaction of a series of coumarin-3-carboxylate and 3-benzoyl coumarins with tert-butyl 2-bromoacetate could give rise to the corresponding cyclopropa[c]coumarins bearing three continuous chiral stereocenters in 83-93% ee and 90-97% ee, respectively. The reaction is proposed to proceed via an in situ generated ammonium ylide intermediate.
ABSTRACT
Cysticercosis is a cosmopolitan zoonotic parasitic disease infected by larval of Taenia solium (T. solium). Several drugs for the treatment of cysticercosis, such as praziquantel, albendazole, and mebendazole, have certain toxicity and side effects. Considering that there is no vaccine available, we studied a new vaccine for cysticercosis in this study. The complete TSOL18 gene and the optimized SP-TSOL18 gene fragments were obtained using PCR-based accurate synthesis method. The secretory and intracellular recombinant pMG36e-SP-TSOL18/Lactococcus lactis (L. lactis) and pMG36e-TSOL18/L. lactis vaccines of T. solium were prepared. Immune responses in mice orally immunized with these two recombinant L. lactis vaccines were analyzed by the determination of specific antibodies (IgG, IgG1, IgG2a, and sIgA) in serum, spleen lymphocyte proliferation, and cytokines (IL-2, IFN-γ, IL-4, and IL-10) in spleen lymphocyte culture supernatant. Our results showed that, after the first immunization, in these two recombinant L. lactis vaccine groups, the levels of serum specific IgG, IgG2a, and IgG1 increased on 14-56 d and reached the highest level on days 42, 42, and 28, respectively. The level of specific sIgA of intestinal mucosa also increased on 14-56 d and reached the highest level on day 42. The level of spleen lymphocyte proliferation increased on 14-56 d and reached the highest level on day 42. The levels of IL-2, IFN-γ, IL-4, and IL-10 in spleen lymphocyte culture supernatant increased on 14-56 d and reached the highest level on days 42, 42, 28, and 28, respectively. These results indicated that the recombinant pMG36e-SP-TSOL18/L. lactis and pMG36e-TSOL18/L. lactis vaccines can induce specific cellular, humoral, and mucosal immune responses in mice with oral vaccination. More importantly, the recombinant pMG36e-SP-TSOL18/L. lactis vaccine has a better immune effect. In summary, these results demonstrated the possibility of using L. lactis strain as a vector to deliver protective antigens of T. solium.
